VCP interaction with HMGB1 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway

• DOI: 10.1186/s12967-022-03416-5
• Publication Date: 2022-05-13T11:09:48Z
• Authors: Zhangya Pu; Dan G. Duda; Yuanyuan Zhu; Siya Pei; Xiaofang Wang; Yan Huang; Panpan Yi; Zebing Huang; Fang Peng; Xingwang Hu; Xuegong Fan
• Keywords: HMGB1

Abstract Background Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer. Valosin-containing protein (VCP) a member AAA-ATPase family associated with multiple molecular functions and involved in tumor metastasis prognosis. However, role VCP HCC progression still unclear. Methods We examined expression using RNA sequencing microarray data from public databases measured it clinical samples cell lines by western blot, immunohistochemistry (IHC). also evaluated correlation between features. The VCP-interacting proteins were identified co-immunoprecipitation combined mass spectrometry (CoIP/MS). underlying mechanisms investigated vitro vivo models HCC. Results found that significantly increased tissues advanced TNM stages poorer prognosis patients. In analyses revealed overexpression promoted proliferation, migration, invasion via PI3K/AKT/mTOR pathway activation. Conversely, knockdown resulted reverse phenotypes. studies indicated up-regulated accelerated growth subcutaneous model. D1 domain A box HMGB1 as critical regions for their interaction, area was required tumor-promoting effects induced expression. enhanced stability decreasing its degradation ubiquitin–proteasome process. Inhibition markedly attenuated VCP-mediated downstream activation signals. Conclusion Collectively, these findings demonstrate potential prognostic biomarker exhibits oncogenic roles played an essential progression, indicating are therapeutic targets human